HS-20093, a novel B7-H3-targeted antibody-drug conjugate (ADC), has shown promising results in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC). Data from the phase 1 ARTEMIS-001 trial (NCT05276609), presented at the 2024 IASLC World Conference on Lung Cancer, indicate that HS-20093 induces significant responses in this patient population.
Efficacy of HS-20093 in ES-SCLC
The ARTEMIS-001 trial, a multicenter, open-label study, evaluated HS-20093 in patients with advanced solid tumors, including ES-SCLC. Patients enrolled in the ES-SCLC cohort had received prior platinum-based chemotherapy with or without immunotherapy, with a limit of three prior lines of therapy. Notably, patients with treated or stable brain metastases were allowed to enroll, and B7-H3 expression was not a selection criterion.
In the dose expansion phase (phase 1b), patients with ES-SCLC were randomized 1:1 to receive HS-20093 at either 8.0 mg/kg or 10.0 mg/kg once every three weeks. The primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1 criteria. Secondary endpoints included safety, pharmacokinetics, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
The results showed that patients treated with HS-20093 at 8 mg/kg (n = 31) achieved an ORR of 61.3% (95% CI, 42.2%-78.2%), while those treated at 10 mg/kg (n = 22) experienced an ORR of 50.0% (95% CI, 28.2%-71.8%). The DCR was 80.6% (95% CI, 62.5%-92.5%) for the 8.0-mg/kg cohort and 95.5% (95% CI, 77.2%-99.9%) for the 10.0-mg/kg cohort.
According to Dr. Jie Wang, MD, PhD, of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, "HS-20093 demonstrated encouraging antitumor efficacy in ES-SCLC and has a higher ORR at the 8.0-mg/kg dose, even though this dose cohort had a higher proportion of patients with brain, liver, and bone metastases."
Duration of Response and Survival
The median DOR was 6.4 months (95% CI, 4.2-12.7) in the 8.0-mg/kg cohort and 8.9 months (95% CI, 2.7-NA) in the 10.0-mg/kg cohort. Patients in the 8.0-mg/kg cohort achieved a median PFS of 5.9 months (95% CI, 4.4-8.5), and those in the 10.0-mg/kg cohort experienced a median PFS of 7.3 months (95% CI, 3.4-11.0). The median OS was 9.8 months (95% CI, 8.5-NA) and not reached in the 8.0-mg/kg and 10.0-mg/kg groups, respectively.
Safety Profile
The most common treatment-related adverse effects (AEs) reported in at least 20% of patients included anemia (any-grade, 85.7%; grade ≥ 3, 16.1%), decreased white blood cell count (80.4%; 33.9%), decreased neutrophil count (67.9%; 39.3%), and decreased platelet count (53.6%; 17.9%). Other common AEs included nausea, pyrexia, and decreased appetite. Dr. Wang noted that "Compared with the 10.0-mg/kg dose, the 8.0-mg/kg dose had a better safety profile in terms of hematologic AEs. No new safety signals were identified."
B7-H3 Expression and Response
Interestingly, the study found a low correlation between tumor B7-H3 expression and tumor objective response. In the 8.0-mg/kg cohort, patients with B7-H3 expression less than 1% (n = 8) experienced an ORR of 75.0% (95% CI, 34.9%-96.8%), while those with expression between 1% and 100% (n = 21) had an ORR of 61.9% (95% CI, 38.4%-81.9%; P = 0.67). Similar trends were observed in the 10.0-mg/kg cohort.
Implications for ES-SCLC Treatment
These findings suggest that HS-20093 is a promising therapeutic option for patients with pretreated ES-SCLC, offering a potential new approach to address this aggressive cancer. Further studies are warranted to confirm these results and to optimize the dosing regimen.
